Alzheimer's Disease Related Copper(II)‐ β‐Amyloid Peptide Exhibits Phenol Monooxygenase and Catechol Oxidase Activities

Abstract

A gray area in gray matter: The CuII complex of a truncated β‐amyloid, CuAβ1–20, catalyzes the oxidation of catechol and the hydroxylation and oxidation of phenol (see picture) with dramatic rate accelerations (≈105–106‐fold increases). The Cu–oxygen chemistry of CuAβ may offer both a better understanding of the chemical effect in the brains of patients who suffer from Alzheimer's disease as well as possible treatment strategies of this disease.

Radioligand Development for PET Imaging of β-Amyloid (Aβ)-Current Status

“…One is the separation of its two negative charges by a fixed distance and the other is the biaryl core organic framework. Titration of radiolabeled CR with A 40 aggregates gave Kd values ranging from 1,100 to 1,500 nM, which are lower than those from a radioligand assay (Ki around 8,000 nM) performed with slightly different A [34][35][36][37][38][39][40][41][42] aggregates. However, when the reference radioligand is changed to chrysamine G (CG; 18), the Ki value of CR changes to 48 nM, representing more than 20-fold higher affinity.…”

“…Metalloelements coordination of Cu and Fe have been demonstrated to co-localize with some of amyloid plaques [35]. Their potential role in the plaque formation and oxidative stress has been studied in vitro [36,37]. The Cu-adducts show catecholase activity, catechol oxidase activity, or tyrosinase activity ascribed to a binuclear form of the Cu II 2 μ 1 : 1 -peroxo, Cu II 2 μ 2 : 2 -peroxo, or Cu II 2 -bis-μ-oxo intermediates [38,39].…”

Tuning the coordination properties of multi-histidine peptides by using a tripodal scaffold: solution chemical study and catechol oxidase mimicking

“…31 Copper(II) bound to different fragments of Aβ has been reported to have phenol and catechol oxidase-like activity, too. [32][33][34] However, such activity was questioned recently, and attributed to the presence of the Scheme 1 Schematic structure of the studied ligands.…”

“…Although a number of reports has been published on the SOD mimicking properties of copper(II)-peptide complexes, [10][11][12] only a few can be found on their oxidase activity. 9,13,[29][30][31][32][33][34][35][36][37] Several copper(II)-bound ATCUNtype peptides are able to oxidatively cleave DNA. 13,29 Copper(II) complexes of amyloid β 1-42 peptide (Aβ) promote oxidative damage to lipid membranes in presence of ascorbate, 30 while the dimeric adduct of Cu(II)-Aβ is able to oxidize cholesterol.…”

Comparison of Two Methods for the Estimation of Stability of Copper(II) Bis-Complexes with Aromatic Ligands Relevant to Alzheimer’s Disease

“…The second, more vital, infl uence of copper in the development of AD is the reduction of Cu 2+ to Cu + via the Aβ peptide. This process directly produces hydrogen peroxide (15) and, subsequently, reactive oxygen species (ROS) (16,17). Copper(II) chelators, especially ligands capable of binding to the Aβ peptide, are therefore viewed as potential drugs and diagnostic tools for the treatment of AD (18,19).…”